ME/CFS Research: Herpes Autoimmune Spectrum Disorder

[Learner1]

Just spotted this article, published in March - https://www.researchgate.net/publication/350541876_Insights_into_Metabolite_Diagnostic_Biomarkers_for_Myalgic_EncephalomyelitisChronic_Fatigue_Syndrome

Section 3 discusses human markers that match the markers I also discuss.

That paper also says this:

"Based on the two kinds of metabolite concentration ratios (pyruvate/isocitrate and ornithine/citrulline) reported by Yamano et al., which indices [whether the energy-producing system (glycolysis/TCA cycle) or the urea cycle], have undergone functional impairment can be predicted, and this might lead to the realization that personalized medicine is best suited for the problem(s) of each patient."

 

[godlovesatrier]

Hi Joshua,

I contacted a consultant nutritionist in the UK who I've used before. She checked various labs for the PAGN test, but it didn't appear in any of the labs. She think it's a specialised urine test. How were you able to obtain this one? I noticed the other test you recommend is over £600, which is completely prohibitive for almost everyone.

Thanks,

 

[lenora]

Hello @joshua.leisk.....Thanks for sending the link to what seemed to work for you. So many, many different topics to read about.

Since I've had this for a long time, I've tried many of the substances suggested. Have they helped? I honestly couldn't tell you....I wish I could be clearer on this matter.

I can tell that you've put a lot of time and effort in this research...and I thank-you. Yours, Lenora.

 

[lenora]

Get the Shingrix vaccine to prevent more attacks.

Yes, @gbells....As soon as the Shingrix vaccine was announced, we were in line for it. It's something like 95% effective, and we had two separate injections and that was a huge sigh of relief. I would recommend it to anyone....don't wait until Shingles attacks. Yours, Lenora.

 

[godlovesatrier]

The non live vaccine is pricey! £525. But I've no doubt it is so completely worthit. Apparently that vaccine gives immunity for up to 20 years, or more after vaccination.

 

[lenora]

Here Medicare covers the cost of the vaccine. I was surprised at how many people were in line for it. Rather reminded me of COVID. We didn't have a live vaccine. Wishing you well. Yours, Lenora.

 

[godlovesatrier]

My uncles had shingles. I definitely don't fancy it.

 

[lenora]

No, you definitely don't want shingles. If nothing else will take you out, that illness will. I had it three times in a row about 7+- yrs. ago, and once in my 30's. It is caused by stress...good or bad, so figure that one out.

The antivirals had only just been introduced at the time my flare-ups began. I was bedridden for about a year, and still haven't returned to being able to do what I could before.

I would encourage anyone over the age of 50 (the age recommended) here to definitely get the vaccine. The side-effects were no worse whatsoever than my Pfizer vaccines for COVID. My husband was the same.

I'm sure you know this, but for those who don't, the anti-virals have to be started within 3 days of the illness. They help considerably, but don't take away all of the symptoms.

Hard to believe all this difficult could be caused by the chicken pox virus staying hidden in one's spinal cord, isn't it? I hope you never have it. Yours, Lenora.

 

[joshua.leisk]

In order to follow the reishi/green tea, etc protocol, do we need to stop all other supplements and medications?

This question should probably be answered by your doctor.

In general, the people who have reached remission so far have successfully discarded their other supplements and medications, apart from eg. the slow and horrible process of withdrawing from benzodiazepines.

(This is now an area I’m also focusing on, as it’s a horrendous withdrawal experience and many CFS/ME people have been caught in the benzo trap. Currently exploring imidazenil and oleamide as therapeutic adjuncts to the tapering process, but as yet, I have no specific advice on an optimal method.)

 

[joshua.leisk]

Hi Joshua,

I contacted a consultant nutritionist in the UK who I've used before. She checked various labs for the PAGN test, but it didn't appear in any of the labs. She think it's a specialised urine test. How were you able to obtain this one? I noticed the other test you recommend is over £600, which is completely prohibitive for almost everyone.

Thanks,

Yes, it’s frustrating. The urine test is currently not common, so it’ll be expensive. I found one US provider offering it - https://www.bcm.edu/research/medical-genetics-labs/test_detail.cfm?testcode=4651&show=1

I’ll look for more options on the other side of the pond.

 

[godlovesatrier]

Thanks for the link.

 

[splusholia]

This question should probably be answered by your doctor.

I guess I meant more in theoretical terms - are there interactions? Not specific advice as to my own supplements.

 

[joshua.leisk]

I guess I meant more in theoretical terms - are there interactions? Not specific advice as to my own supplements.

There are a few surprising "known" ones -

1. Tylenol - it causes a similar issue at a-KGDH.
2. NAD+/NMN/NR - this is an interesting one, as it acts as a directional lever between glutamate and aKG. Anyone on eg. benzodiazapines may find this particularly problematic.
3. Various large doses of things that can be used for anaplerosis (feeding the mitochondria through other reactions). This can be problematic if the mitochondria are being "overfed". The NutrEval reports can show this as a "high" marker in various places of the cycle. This alone can lead to PEM. Tricky balance. One your ROS is high, the oxidative stress causes a-KGDH to drop, leading to transamination. It snowballs from there.
4. Acetyl-L-Carnitine - this one may be okay in smaller doses.

I'm currently putting together various lists.

One of them is a list of other pathogens which can induce CFS/ME symptoms.

HHV seems straightforward now. I need to look at eg. coxsackie, parvo-b19 and a number of others. One of the annoying things I can already see ahead is that people with co-infections are going to start treating their HHV and still be left with issues from a secondary infection. I have a "no person left behind" approach here. We need better pathology data and ways to quantify the causal factors, to effectively help people.

According to our research, CFS/ME can be caused by a number of issues.

1. ⁠Anything that increases glutamate dehydrogenase (HHV, C.diff)
2. ⁠Anything that depletes glutamine (HHV), which triggers mitochondrial fusion.
3. ⁠Anything which breaks the reaction at a-KGDH (high dose Tylenol / acetylsalicate).
4. ⁠Anything that causes hypoxia. eg. Arsenic.
5. ⁠Anything that breaks Acetyl-CoA metabolism, eg. LPS-positive bacterial infection.
6. ... other vectors I'm still exploring.

Another is a list of supplements which can influence important aspects of related metabolism.

If you or anyone else want to contribute ideas about common supplements or drugs to include in that research, I'm happy to explore them and document accordingly.

 

[dannybex]

That paper also says this:

"Based on the two kinds of metabolite concentration ratios (pyruvate/isocitrate and ornithine/citrulline) reported by Yamano et al., which indices [whether the energy-producing system (glycolysis/TCA cycle) or the urea cycle], have undergone functional impairment can be predicted, and this might lead to the realization that personalized medicine is best suited for the problem(s) of each patient."

Ding-ding-ding. I think most patients, or the majority of patients -- at least on Phoenix Rising -- have found this to be true. We all got sick in different ways, so we'll each need to utilize different ways to get better.

 

[Learner1]

There are a few surprising "known" ones -

1. Tylenol - it causes a similar issue at a-KGDH.
2. NAD+/NMN/NR - this is an interesting one, as it acts as a directional lever between glutamate and aKG. Anyone on eg. benzodiazapines may find this particularly problematic.
3. Various large doses of things that can be used for anaplerosis (feeding the mitochondria through other reactions). This can be problematic if the mitochondria are being "overfed". The NutrEval reports can show this as a "high" marker in various places of the cycle. This alone can lead to PEM. Tricky balance. One your ROS is high, the oxidative stress causes a-KGDH to drop, leading to transamination. It snowballs from there.
4. Acetyl-L-Carnitine - this one may be okay in smaller doses.

I'm currently putting together various lists.

One of them is a list of other pathogens which can induce CFS/ME symptoms.

HHV seems straightforward now. I need to look at eg. coxsackie, parvo-b19 and a number of others. One of the annoying things I can already see ahead is that people with co-infections are going to start treating their HHV and still be left with issues from a secondary infection. I have a "no person left behind" approach here. We need better pathology data and ways to quantify the causal factors, to effectively help people.

According to our research, CFS/ME can be caused by a number of issues.

1. ⁠Anything that increases glutamate dehydrogenase (HHV, C.diff)
2. ⁠Anything that depletes glutamine (HHV), which triggers mitochondrial fusion.
3. ⁠Anything which breaks the reaction at a-KGDH (high dose Tylenol / acetylsalicate).
4. ⁠Anything that causes hypoxia. eg. Arsenic.
5. ⁠Anything that breaks Acetyl-CoA metabolism, eg. LPS-positive bacterial infection.
6. ... other vectors I'm still exploring.

Another is a list of supplements which can influence important aspects of related metabolism.

If you or anyone else want to contribute ideas about common supplements or drugs to include in that research, I'm happy to explore them and document accordingly.

HHV6 promotes mitochondrial fragmentation, not fusion, according to recent research:

https://www.immunohorizons.org/content/4/4/201

It would be great if you can include vitamins A, C, D, E, K, B1, B2, B5, B6, biotin, folate, B12, glycine, lysine, methionine, tyrosine, copper, manganese, selenium, zinc, omega 3s, phospholipids - phosphatidyl choline, ethanolamine, inositol, and serine.

Great work - thanks!

 

[joshua.leisk]

HHV6 promotes mitochondrial fragmentation, not fusion, according to recent research:

https://www.immunohorizons.org/content/4/4/201

It would be great if you can include vitamins A, C, D, E, K, B1, B2, B5, B6, biotin, folate, B12, glycine, lysine, methionine, tyrosine, copper, manganese, selenium, zinc, omega 3s, phospholipids - phosphatidyl choline, ethanolamine, inositol, and serine.

Great work - thanks!

Yes - mitochondrial fusion: I haven't seen a single person's lab result where this looks like it has occurred (at least from the plasma profiles). I mentioned it more for completeness in the 3rd paper.

One of other my current tasks (for which I'm enjoying input from some very helpful community members) is to create a comprehensive list of individual symptoms / pathway impacts (basically the 100 or so pathways I [...] in the third paper, while discussing the metabolite depletion cascade downstream of the phenylacetylglutamine (PAGN) pathway overload and Reactive Oxygen Species (ROS).)

This document can ultimately be used by individuals or clinicians to commence a personalised treatment plan that addresses individual circumstances and then creates a homogenized process to follow on with.

On that note, we also discovered today that the NutrEval FMV report has the markers needed to identify ammonia metabolism via PAGN activity and benzoate->hippurate. This is amazing! Solves the problem with only one provider in the US testing for PAGN. It also has urea.

This will be confounded by dietary input and microbiome to some extent, however that's the same for the other PAGN test.

Also, regarding ROS and EGCG. I made previous comments in the 3rd paper and some other places about the impact of high GI carbs and sugars in this disease model. I realised that the dose range of EGCG is quite critical to ROS prevention. If the EGCG dose is too high (so too low GDH), then any "excess" pressure from high blood glucose and potentially full glycogen stores will create additional ROS in the same way that having too high GDH will, just from the other side of the cycle. Excess energy can't be diverted at aKG to glutamate. ALT will elevate, showing this.

The ideal EGCG dose may be closer to 20-25mg, every 4.5 hours.

With that in mind, the ideal "safe" CFS/ME diet will be similar to the one I mentioned in the 3rd paper - high fat, low net carb (50-85g), low sugar, moderately high protein - even when on v3 of the protocol.

 

[joshua.leisk]

Updated the pilot spec to v3.1 - https://www.researchgate.net/public...for_Rapid_Testing_of_HASD_CFSME_Disease_Model

 

[YippeeKi YOW !!]

@Rebeccare , @Rufous McKinney , @Howard , @ljimbo423 , @Haley , @Blue Jay , @Rebecca under the papyrus , @Judee , @Art Vandelay , @Hip , @Hipsman , @IThinkImTurningJapanese .....

More tag-ins will follow as I try to drop-kick my brain, and the gopher wheel that currently runs it, into action ....

This is a staggering amount of information, both in scope, depth, width and breadth, and written and presented so lucidly and so beautifully that I’m speechless.

Ask anyone in these threads: that’s not my usual response .

I’m equally impressed, perhaps even more so if that’s possible, by the character and nature of the presenter, @joshua.leisk and his unnamed life partner, whose contributions Joshua makes clear are invaluable.

The effort taken to make this depth of information accessible to almost anyone who can read, even in the small increments some of us have to apply to new input and information, and use the Google machine indicates someone whose interests lie a good distance from material gain or ego enrichment, but indicate instead a high intelligence and a genuinely questing mind and spirit, with the willingness and drive to put those gifts at the service of others. And to do so with grace and great wit, two other characteristics not usually in abundant display in the scientific and medical community.

DO START AT THE FIRST POST .... it's the woof/warp and weft for all that follows .... or, probably even better, here's a more user-friendly version that @joshua.leisk and Aline Nocon prepared especially for those of us who are more science-ly or brain fog impaired, or, if we're really firing on no cyclinders, both, simultaneously ....

Give it a browse ....

CFS/ME: A New Hope
https://www.researchgate.net/publication/350956432_CFSME_A_New_Hope

 

[Rufous McKinney]

to almost anyone who can read, even in the small increments

This all looks brilliant and fascinating and, well I hope to read thru it in small increments, also

Anyone able to distill this into an essence- usable essence- let me know!

 

[YippeeKi YOW !!]

Anyone able to distill this into an essence- usable essence- let me know!

Too complex and multi-layered for that .....no CLiff notes .... just browse thru it at whatever pace is comfy for you, and see what leaps out at you ...

OK, because it's you, here's a more user-friendly version that @joshua.leisk and Aline Nocon prepared especially for those of us who are more science-ly or brain fog impaired, or, if we're really firing on no cyclinders, both, simultaneously ....

Give it a leisurely browse ....

CFS/ME: A New Hope
https://www.researchgate.net/publication/350956432_CFSME_A_New_Hope